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Informations
Publié par | johannes_gutenberg-universitat_mainz |
Publié le | 01 janvier 2010 |
Nombre de lectures | 36 |
Langue | Deutsch |
Poids de l'ouvrage | 22 Mo |
Extrait
Sensitivity enhancement in NMR by
using parahydrogen induced
polarization
Dissertation zur Erlangung des Grades
Doktor der Naturwissenschaften
am Fachbereich Chemie
der Johannes Gutenberg-Universitat¨
in Mainz
Meike Roth
geboren in Mainz
Mainz 2010Die vorliegende Arbeit wurde in der Zeit von September 2007 bis April 2010 am
Max-Planck-Institut fur¨ Polymerforschung in Mainz angefertigt.
Dekan:
Erster Berichterstatter:
Zweiter
Tag der mundlichen¨ Prufung:¨ 21.05.2010”Es kommt nicht darauf an, mit dem Kopf durch die Wand zu rennen,
sondern mit den Augen die Tur¨ zu finden.”
Albert EinsteinContents
1 Introduction 1
2 Theory 4
2.1 Hyperpolarization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2.2 Parahydrogen Induced Polarization . . . . . . . . . . . . . . . . . . . . . 5
2.2.1 Ortho- and Parahydrogen . . . . . . . . . . . . . . . . . . . . . . . 6
2.2.2 The Chemical Reaction behind the PHIP Method . . . . . . . . . 10
2.2.3 Density Matrix Approach . . . . . . . . . . . . . . . . . . . . . . . 16
2.2.4 Theorectical Signal Enhancement . . . . . . . . . . . . . . . . . . . 18
2.2.5 Relaxation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2.6 Transfer of Polarization to Heteronuclei . . . . . . . . . . . . . . . 22
3 Optimizing the Parahydrogen Technique on Model Compounds 24
3.1 Model Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.1.1 1-Hexyne . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.1.2 2-Hydroxyethyl acrylate . . . . . . . . . . . . . . . . . . . . . . . . 27
3.2 Parahydrogen Generation . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.3 Catalytic Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
3.3.1 Water-insoluble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
3.3.2 Water-soluble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3.4 Hydrogenation Conditions and Different Ways to Apply Parahydrogen 41
3.4.1 The Standard PASADENA Experiment . . . . . . . . . . . . . . . 41
3.4.2 ALTADENA and P under Pressure . . . . . . . . . . . 43
3.4.3 PASADENA with Membranes . . . . . . . . . . . . . . . . . . . . 44
3.5 Polarization Transfer to Heteronuclei . . . . . . . . . . . . . . . . . . . . . 53
3.5.1 Spontaneous Polarization Transfer at low Field . . . . . . . . . . . 53
3.5.2 Polarization transfer via INEPT(+p/4) and PH-INEPT+ Sequences 56
3.5.3 Combination with the Membrane Setup . . . . . . . . . . . . . . . 62II Contents
4 Physiologically Relevant Substances for PHIP 67
4.1 Metabolites and Neurotransmitters . . . . . . . . . . . . . . . . . . . . . . 68
4.1.1 Towards Metabolites of the Citric Acid Cycle . . . . . . . . . . . . 68
4.1.2 GABA and its Derivatives . . . . . . . . . . . . . . . . . . . . . . . 81
4.2 Drugs and Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . 85
4.2.1 Hyperpolarization of a Barbituric Acid derivative . . . . . . . . . 85
4.2.2 Citalopram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
4.3 Polymerizable Monomers . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.3.1 N-Vinyl-2-pyrrolidone . . . . . . . . . . . . . . . . . . . . . . . . . 101
5 Conclusion 111
6 Appendix 117
6.1 General Experimental Parameters . . . . . . . . . . . . . . . . . . . . . . . 117
6.2 Parahydrogen Enrichment . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
6.3 Sample Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
6.4 Calculation of Signal Enhancements . . . . . . . . . . . . . . . . . . . . . 119
6.5 T Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1211
6.6 Synthesis of Model Compounds . . . . . . . . . . . . . . . . . . . . . . . . 122
6.6.1 5-Methyl-5-propenyl-barbituric acid . . . . . . . . . . . . . . . . . 122
136.6.2 C-acetylenedicarboxylic acid dimethyl ester . . . . . . . . . . . 126
6.6.3 1-Allyl-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile 130
6.7 Synthesis of a Water-soluble Ligand System . . . . . . . . . . . . . . . . . 132
6.7.1 Tppsm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132Abbreviations
ALTADENA adiabatic longitudinal transport after dissociation engenders
net alignment
BAC biologically active compound
CACA cis-4-amino-crotonic acid
CAS chemical abstracts-number
COD cyclooctadiene
COSY correlation spectroscopy
d doublet
dd of doublets
DNP dynamic nuclear polarization
dppb (diphenylphosphino)butane
dppbs [diphenyl-sulfonate)phosphine]butane
e.g. exempli gratia
FD field desorption
FID free induction decay
FT fourier transformation
GABA g-aminobutyric acid
i.e. id est
INEPT insensitive nuclei enhancement by polarisation
IR infrared
IUPAC international union of pure and applied chemistry
LDA lithium diisopropylamide
m multiplet
MHz megahertz
MRI magnetic resonance imaging
MS mass spectrum
NMR nuclear magnetic resonance
NOE Overhausen effect
nor norbonadiene
NVP N-vinyl-2-pyrrolidoneIV Abbreviations
o-H orthohydrogen2
p-H parahydrogen2
PASADENAogen and synthesis allow dramatically enhanced nu-
clear alignment
Pgp permeability glycoprotein
PH-INEPT parahydrogen-insensitive nuclei enhancement by polarisation
PHIPogen induced polarization
Photo-CIDNP photochemically induced dynamic nuclear polarization
ppbs (phenyl-propane sulfonate)phosphine
ppm parts per million
PVP polyvinylpyrrolidone
pyr pyridine
qu quartet
rf radio frequency
s singlet
SE signal enhancement
SNR signal-to-noise ratio
SSRIs selective serotonin reuptake inhibitors
t triplet
TACA trans-4-amino-crotonic acid
tchp tricyclohexylphosphine
tdmpp tris(dimethyl-phenylphosphine)
TPA time point of acquisition
tpps [triphenyl-sulfonate phosphine)
tppsm triphenyl-sulfonate-methoxy phosphine)